Brain γ-aminobutyric acid (GABA) detection in vivo with the J-editing (1) H MRS technique: a comprehensive methodological evaluation of sensitivity enhancement, macromolecule contamination and test-retest reliability.

Abnormalities in brain γ-aminobutyric acid (GABA) have been implicated in various neuropsychiatric and neurological disorders. However, in vivo GABA detection by (1) H MRS presents significant challenges arising from the low brain concentration, overlap by much stronger resonances and contamination by mobile macromolecule (MM) signals. This study addresses these impediments to reliable brain GABA detection with the J-editing difference technique on a 3-T MR system in healthy human subjects by: (i) assessing the sensitivity gains attainable with an eight-channel phased-array head coil; (ii) determining the magnitude and anatomic variation of the contamination of GABA by MM; and (iii) estimating the test-retest reliability of the measurement of GABA with this method. Sensitivity gains and test-retest reliability were examined in the dorsolateral prefrontal cortex (DLPFC), whereas MM levels were compared across three cortical regions: DLPFC, the medial prefrontal cortex (MPFC) and the occipital cortex (OCC). A three-fold higher GABA detection sensitivity was attained with the eight-channel head coil compared with the standard single-channel head coil in DLPFC. Despite significant anatomical variation in GABA + MM and MM across the three brain regions (p < 0.05), the contribution of MM to GABA + MM was relatively stable across the three voxels, ranging from 41% to 49%, a non-significant regional variation (p = 0.58). The test-retest reliability of GABA measurement, expressed as either the ratio to voxel tissue water (W) or to total creatine, was found to be very high for both the single-channel coil and the eight-channel phased-array coil. For the eight-channel coil, for example, Pearson's correlation coefficient of test vs. retest for GABA/W was 0.98 (R(2) = 0.96, p = 0.0007), the percentage coefficient of variation (CV) was 1.25% and the intraclass correlation coefficient (ICC) was 0.98. Similar reliability was also found for the co-edited resonance of combined glutamate and glutamine (Glx) for both coils. Copyright © 2016 John Wiley & Sons, Ltd.

[11C]NNC 112 selectivity for dopamine D1 and serotonin 5-HT(2A) receptors: a PET study in healthy human subjects.

The dopamine D(1) receptor antagonist radioligand [(11)C]NNC 112 has previously been reported to have 100-fold selectivity for the D(1) receptor compared with the serotonin 5-HT(2A) receptor. In this study, we tested the selectivity by scanning seven healthy human research volunteers with [(11)C]NNC 112 before and after 2 mg of the antipsychotic drug risperidone, a dose that putatively blocks all 5-HT(2A) receptors with negligible effect on D(1) receptors. We found that specific binding in cortical regions was reduced by 20% to 30%, whereas the striatum showed no change. Based on the known relative densities of these receptors in humans, our results suggest 5- to 10-fold selectivity of [(11)C]NNC 112 for D(1) versus 5-HT(2A) as opposed to 100-fold selectivity. These results suggest caution in interpreting data from studies using this tracer to measure cortical D(1) receptors as well as the need for more selective radioligands to assess cortical D(1) receptors.

Relationship Between Meal Plan, Dietary Intake, Body Mass Index, and Appetitive Responsiveness in College Students.

INTRODUCTION: One third of the approximately 23,000 undergraduates in the United States are overweight or obese. College students appear to be more vulnerable to disproportionate weight gain during this time. METHOD: Cross-sectional. Diet, body mass index, and appetitive responsiveness were assessed in 80 undergraduates enrolled in three different meal plans, unlimited access, points, and none. RESULTS: Appetitive responsiveness was positively correlated with fat (r = 0.34, p = .002) but not added sugars across groups. Unlimited access-plan students had higher fat consumption than no-plan students, regardless of appetitive responsiveness. Unlimited access-plan students had higher fruit and vegetable consumption and higher dairy consumption than point-plan students. There were no group differences for body mass index. All groups were below the U.S. Department of Agriculture guidelines for dairy and fruit and vegetable intake. DISCUSSION: Optimizing the college campus food environment toward healthful, affordable choices is likely to improve dietary habits and might minimize college weight gain.

Dose-occupancy study of striatal and extrastriatal dopamine D2 receptors by aripiprazole in schizophrenia with PET and [18F]fallypride.

Positron emission tomography (PET) and the high affinity D(2/3) radiotracer [(18)F]fallypride allow the assessment of D(2/3) receptor occupancy of antipsychotic drugs in striatal and extrastriatal brain regions. We measured regional occupancy attained across a range of clinical dosing by the partial D(2) agonist aripiprazole using these methods. Twenty-eight PET scans were acquired on the ECAT EXACT HR+ camera in 19 patients with schizophrenia or schizoaffective disorder. Daily aripiprazole doses ranged from 2 to 40 mg, with a minimum of 10 days on steady dose. Mean regional occupancies, a model-independent estimate of aripiprazole effect on pituitary binding, and PANSS ratings changes were evaluated. Occupancy levels were high across regions of interest, ranging from 71.6+/-5.5% at 2 mg/day to 96.8+/-5.3% at 40 mg/day. Occupancy levels were higher in extrastriatal than striatal regions. Pituitary measures of aripiprazole effect correlated with doses and were unrelated to prolactin levels, which remained within the normal range under medication. PANSS positive (but not negative) symptom improvement correlated with striatal but not extrastriatal occupancies. These data show, for the first time, D(2) occupancy by aripiprazole in treated patients with schizophrenia in extrastriatal as well as striatal regions, with high occupancy for all doses. We discuss possible explanations for higher extrastriatal than striatal occupancy. Correlations of ratings of clinical improvement with regional occupancy suggest that aripiprazole, as do other antipsychotics, benefits positive symptoms of schizophrenia most directly through its modulation of striatal rather than cortical or other extrastriatal dopamine activity.